The present investigation has been undertaken to evaluate the role of Spirulina fusiformis in modifying the mercury-induced biochemical alterations in Swiss albino mice. Animals were divided into four groups: (i) control group - only vehicle (0.9% NaCl/olive oil) was given; (ii) HgCl(2) treated group - 5.0mg/kg b.w. HgCl(2) administered as i.p.; (iii) Spirulina treated group - 800mg/kg b.w. Spirulina extract was administered orally; (iv) combination group -S. fusiformis was administered 10 days before mercuric chloride administration and continued up to 30 days after mercuric chloride administration (5.0mg/kg b.w.). The animals were sacrificed on 1, 3, 7, 15 and 30 days and the activity of serum alkaline and acid phosphatase, serum iron level, serum calcium level, blood lipid peroxidation content and blood glutathione (GSH) level were measured. In the present investigation, mercury intoxication causes significant increase (P<0.001) in calcium level, acid phosphatase and lipid peroxidation content and significant decrease in iron level, alkaline phosphatase and glutathione level. Spirulina pre- and post-treatment with mercury prevented or reduces mercury-induced alterations in terms of calcium level, iron level, acid and alkaline phosphatase activity in serum, and lipid peroxidation and GSH level in blood. Thus from the present investigation, it can be concluded that Spirulina pre- and post-treatment with HgCl(2) significantly modulate or modify mercury-induced biochemical alteration in blood of Swiss albino mice.